Scholarlink

<p>TNBC represents an exceptionally aggressive subtype, distinguished by the absence of targeted therapeutic options. miR-770-5p, a tumor suppressor microRNA, has been shown to regulate critical cancer-associated signaling pathways. PRMT5, is frequently overexpressed in various malignancies and plays a pivotal role in regulating cellular processes, including EGFR signaling, thereby contributing to tumorigenesis. PRMT5 acts as a key modulator of KLF4 transcriptional activity, with its methylation of KLF4, enhancing EGFR expression and promoting tumor progression. In this study, we investigated the regulatory interplay between the PRMT5-KLF4 axis and miR-770-5p in TNBC, focusing specifically on the modulation of EGFR signaling. Bioinformatics analyses identified EGFR as a potential target of miR-770-5p, and experimental validation demonstrated that restoring miR-770-5p expression in TNBC cell lines led to a downregulation of EGFR signaling. Furthermore, our findings unequivocally demonstrate that miR-770-5p directly targets PRMT5, leading to a significant reduction in PRMT5 expression and a notable alteration in KLF4 localization. miR-770-5p treatment increased the cytoplasmic-to-nuclear ratio of KLF4 and disrupted EGFR localization, demonstrating that miR-770-5p disrupts the PRMT5-KLF4-driven activation of EGFR signaling. These findings indicate that miR-770-5p acts as a tumor suppressor in TNBC by modulating EGFR signaling via PRMT5 and KLF4, emphasizing its potential as a therapeutic target.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

miR-770-5p: A novel molecular target regulating KLF4/EGFR signaling through PRMT5 interaction

  • 期刊论文

  • 发表日期：

    2025年11月10日

查看全文
  • Senem Noyan,
  • Bala Gur Dedeoglu,
  • Alp Can,
  • Mehmet Alikasifoglu

摘要

TNBC represents an exceptionally aggressive subtype, distinguished by the absence of targeted therapeutic options. miR-770-5p, a tumor suppressor microRNA, has been shown to regulate critical cancer-associated signaling pathways. PRMT5, is frequently overexpressed in various malignancies and plays a pivotal role in regulating cellular processes, including EGFR signaling, thereby contributing to tumorigenesis. PRMT5 acts as a key modulator of KLF4 transcriptional activity, with its methylation of KLF4, enhancing EGFR expression and promoting tumor progression. In this study, we investigated the regulatory interplay between the PRMT5-KLF4 axis and miR-770-5p in TNBC, focusing specifically on the modulation of EGFR signaling. Bioinformatics analyses identified EGFR as a potential target of miR-770-5p, and experimental validation demonstrated that restoring miR-770-5p expression in TNBC cell lines led to a downregulation of EGFR signaling. Furthermore, our findings unequivocally demonstrate that miR-770-5p directly targets PRMT5, leading to a significant reduction in PRMT5 expression and a notable alteration in KLF4 localization. miR-770-5p treatment increased the cytoplasmic-to-nuclear ratio of KLF4 and disrupted EGFR localization, demonstrating that miR-770-5p disrupts the PRMT5-KLF4-driven activation of EGFR signaling. These findings indicate that miR-770-5p acts as a tumor suppressor in TNBC by modulating EGFR signaling via PRMT5 and KLF4, emphasizing its potential as a therapeutic target.